Dysregulation in the neuroendocrine stress system has been attributed repeatedly to the stressful and anxiogenic state observed during alcohol withdrawal. Activity of the atrial natriuretic peptide (ANP) has been shown to inhibit the release of corticotrophin releasing hormone (CRH) and corticotrophin (ACTH) and opioid neurotransmission also plays a role in counteracting effects of sustained stress by facilitating the termination of the hypothalamo-pituitary-adrenocortical (HPA) axis stress response. Thus ANP and ß-endorphin may be involved in modulating the HPA axis activity in alcohol withdrawal. Aim of the study was to evaluate the anxiolytic activity of ANP and ß-endorphin during alcohol withdrawal in mice habitated to chronic alcohol intake.

24 male mice (C57/Bl6J) were studied following 21 days of free-choice and forced alcohol intake. Anxiety related behavior (elevated plus maze, open field) was tested during acute ethanol withdrawal (12 hours after last ethanol consumption). 30 minutes before testing, randomized groups of mice were given i.p. injections of ANP (60 μg/kg), ß-endorphin (2 μg/kg) or saline.

Acute alcohol withdrawal in alcohol habituated mice was associated with increased anxiety related behavior. Application of both, ß-endorphin and ANP, was significantly associated with reduced anxiety related behavior.

Taking into consideration data from studies in humans, where decreased levels of ß-endorphin and ANP were associated with anxiety during acute and protracted alcohol withdrawal, our results suggest a causal relationship between ANP, ß-endorphin and withdrawal-induced anxiety in alcohol related disorders.